This invention relates to novel compounds which show activity as plant growth regulators, particularly as chemical hybridization agents, to growth regulant compositions which comprise these compounds, and to methods of regulating the growth of plants, particularly by inducing selective male sterility, with these compounds and compositions.
The cereal grains, such as corn, wheat, rice, rye, barley, oats, millets, sorghum, triticale, and terff and forage crops such as those disclosed in Scientific American Vol. 234, pg. 61-69, Feb., 1976 by Harlow J. Hodgson are among the major potential food crops throughout the world. This importance has led to extensive research to improve both the productivity and food value of these crops. One of the most important approaches taken to improve the quality and yield of the cereal grains has been hybridization. While hybridization has been an effective technique for some crops, most notably corn, there have been a number of problems with present techniques. For example, corn hybridization requires time-consuming hand detasseling or inefficient mechanical detasseling, possibly injuring the corn plant. Corn, and wheat hybridization by means of cytoplasmic male sterile varieties can only be done with a limited genetic base, requiring a maintainer line and a restorer line. Furthermore, cytoplasmic male sterile techniques with wheat necessitate a highly sophisticated approach to deal with the genetic complexities of this crop, and great success has not yet been achieved in developing a suitable approach. Since the induction of selective male sterility by chemical means would obviate many of the problems confronting the present hybridization techniques, new compounds which selectively produce the desired sterility would be extremely desirable in dependably and economically supplying the male sterile plants needed for hybridization.
A new class of compounds has now been found which can be used to induce selective male sterility in cereal grains. The compounds of the invention are 1,4-dihydro-4-oxo(thio)-pyridazines having the formula ##STR2## wherein R.sup.1 is phenyl or naphthyl group or a substituted phenyl or naphthyl group, preferably having up to three substitutuents having a total of up to 6 carbon atoms,
R.sup.2 is an alkyl group, preferably having up to 4 carbon atoms, or phenyl, and PA1 R.sup.3 is a hydrogen atom, an alkyl group, preferably having up to 4 carbon atoms, or a halogen atom, preferably a bromine or a chlorine atom, benzyl or phenethyl, or PA1 R.sup.2 and R.sup.3 taken together are --(CH.sub.2).sub.n -- wherein n is an integer from 3 to 8 preferably from 3 to 5, PA1 Z is oxygen or sulfur, and PA1 Y is the group ZR.sup.4 or NR.sup.5 R.sup.6 PA1 wherein
Z' is oxygen or sulfur, PA2 R.sup.4 is a hydrgen atom or an agronomically acceptable salt thereof; an alkyl group preferably having up to 12 carbon atoms most preferably up to 4 carbon atoms; an alkoxyalkyl group preferably having up to 12 carbon atoms most preferably up to 4 carbon atoms; a cycloalkyl group having a carbon atom ring of from 3 to 8 carbon atoms, preferably 6 carbon atoms; a cycloalkylalkyl group having a carbon atom ring of from 3 to 8 carbon atoms preferably 6 carbon atoms and an alkyl chain of up to 4 carbon atoms preferably a methylene group; a haloalkyl group having up to 12 carbon atoms preferably chloro, bromo or iodoalkyl of up to 5 carbon atoms, more preferably bromopropyl, chlorobutyl or iodopentyl; a phenyl, naphthyl or benzyl group or a phenyl, naphthyl or benzyl group substituted with up to three substituents having a total of up to 6 carbon atoms; or a cation,
R.sup.5 and R.sup.6 are independently selected from the group consisting of hydrogen or alkyl of up to 4 carbon atoms or alkyl of up to 4 carbon atoms substituted with carboxy or (C.sub.1 -C.sub.4)alkoxycarbonyl or the agronomically acceptable salt thereof or when R.sup.5 is hydrogen R.sup.6 is hydroxyl or an alkali metal salt thereof.
In a preferred embodiment of the invention, ##STR3## is a carboxy group or a salt thereof, R.sup.2 is a methyl group, R.sup.3 is a hydrogen atom or a halogen atom, and R.sup.1 is a substituted phenyl group.
When the group Y is a salt of a carboxy group, an alkali metal, alkaline earth metal, or transition metal can provide the cation. The cation can also be an ammonium or substituted ammonium group. Representative metal salt cations include alkali metal cations, which are preferred, such as sodium, potassium, lithium, or the like, alkaline earth metal cations, such as calcium, magnesium, barium, strontium, or the like, or heavy metal cations, such as zinc, manganese, cupric, cuprous, ferric, ferrous, titanium, aluminum, or the like.
Among the ammonium salts are those of the formula ##STR4## in which R.sup.7, R.sup.8, R.sup.9 and R.sup.10 are individually a hydrogen atom, a hydroxy group, a (C.sub.1 -C.sub.4)alkoxy group, a (C.sub.1 -C.sub.20)alkyl group, a (C.sub.3 -C.sub.8)alkenyl group, a (C.sub.3 -C.sub.8)alkynyl group, a (C.sub.2 -C.sub.8)hydroxy alkyl group, a (C.sub.2 -C.sub.8)alkoxyalkyl group, a (C.sub.2 -C.sub.6)amincalkyl group, a (C.sub.2 -C.sub.6)haloalkyl group, a substituted or unsubstituted phenyl group, a substituted or unsubstituted phenylalkyl group, having up to 4 carbon atoms in the alkyl moiety, an amino or alkyl-substituted amino group, or any two of R.sup.7, R.sup.8, R.sup.9 or R.sup.10 can be taken together to form with the nitrogen atom a 5- or 6-membered heterocyclic ring, optionally having up to one additional hetero oxygen, nitrogen, or sulfur atom in the ring, and preferably saturated, such as a piperidine, morpholine, pyrrolidine or piperazine ring, or the like, or any three of R.sup.7, R.sup.8, R.sup.9 or R.sup.10 can be taken together to form with the nitrogen atom a 5- or 6-member optionally substituted aromatic heterocyclic ring, such as pyrrole, pyridine, nicotine or histamine. When the ammonium group contains a substituted alkyl, substituted phenyl, or substituted phenylalkyl group, the substituents will generally be selected from halogen atoms, (C.sub.1 -C.sub.8)alkyl groups, (C.sub.1 -C.sub.4)alkoxy groups, hydroxy groups, nitro groups, trifluoromethyl groups, cyano groups, amino groups, (C.sub.1 -C.sub.4)alkylthio groups, and the like. Such substituted phenyl groups preferably have up to two such substituents. Representative ammonium cations include ammonium, dimethylammonium 2-ethylhexylammonium, bis(2-hydroxyethyl)ammonium, t-octylammonium, 2-hydroxyethylammonium, morpholinium, piperidinium, 2-phenethylammonium, 2-methylbenzyl-ammonium, n-hexylammonium, triethylammonium, trimethylammonium, tri(n-butyl)ammonium, methoxy-ethylammonium, diisopropylammonium, pyridinium, diallylammonium, pyrazolium, propargylammonium, dimethylhydrazinium, hydroxyammonium, methoxyammonium, dodecylammonium, octadecylammonium, 4-dichlorophenyl-ammonium, 4-nitrobenzylammonium, benzyltrimethyl-ammonium, 2-hydroxyethyldimethyloctadecylammonium, 2-hydroxyethyldiethyloctylammonium, decyltrimethyl-ammonium, hexyltriethylammonium, 4-methylbenzyltrimethylammonium, and the like.
Representative embodiments of R.sup.1 include phenyl groups substituted with alkyl groups, preferably having up to 4 carbon atoms, aryl groups, preferably phenyl or substituted phenyl groups, alkoxy groups, preferably having up to 4 carbon atoms, phenoxy or substituted phenoxy groups, halogen atoms, such as fluorine, chlorine, bromine, and iodine atoms, nitro groups, perhaloalkyl groups, such as trifluoromethyl groups, alkoxyalkyl groups, preferably having up to 6 carbon atoms, alkoxyalkoxy groups, preferably having up to 6 carbon atoms, amino groups, alkyl or dialkyl amino groups, preferably having up to 4 carbon atoms in each alkyl substituent, cyano groups, carbalkoxy groups, preferably having up to 4 carbon atoms in the alkoxy moiety, carboxy groups, carbamoyl groups, alkyl or dialkyl carbamoyl groups, preferably having up to 4 carbon atoms in each alkyl substituent, sulfo groups, sulfonamide groups, alkylcarbonyl or carboxyalkyl groups, preferably having up to 4 carbon atoms in the alkyl moiety, alkanoyloxy groups, preferably having up to 4 carbon atoms, haloalkyl groups, alkanoylamido groups, preferably having up to 4 carbon atoms, alkylthio groups, preferably having up to 4 carbon atoms, alkylsulfinyl groups, preferably having up to 4 carbon atoms, alkylsulfonyl groups, preferably having up to 4 carbon atoms, and the like. Preferably, the substituted phenyl group will have up to three of the above substituents and the substituents will have a total of up to six carbon atoms. The most preferred substituents on the phenyl group are 1 or 2 halogen atoms, a (C.sub.1 -C.sub.4)alkyl, preferably methyl, group, a (C.sub.1 -C.sub.4)alkoxy, preferably methoxy group, (C.sub.1 -C.sub.4 )alkylthio, (C.sub.1 -C.sub.4)alkylsulfinyl, (C.sub.1 -C.sub.4)alkyl sulfonyl or a trifluoromethyl group.
Typical compounds within the scope of this invention include:
1-phenyl-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(4-bromophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(4-iodophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(3-fluorophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(3-chlorophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(3-bromophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(3,4-dichlorophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(2-fluorophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxlic acid PA0 1-(2-chlorophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(4-trifluoromethylphenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxyl ic acid PA0 1-(3-trifluoromethylphenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxyl ic acid PA0 1-phenyl-1,4-dihydro-4-oxo-6-ethylpyridazine-3-carboxylic acid PA0 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-6-ethylpyridazine-3-carboxylic acid PA0 1-(4-fluorophenyl)-1,4-dihydro-4-oxo-6-ethylpyridazine-3-carboxylic acid PA0 1-(3,4-dichlorophenyl)-1,4-dihydro-4-oxo-6-ethylpyridazine-3-carboxylic acid PA0 1-phenyl-1,4-dihydro-4-oxo-6-propylpyridazine-3-carboxylic acid PA0 1-phenyl-1,4-dihydro-4-oxo-5,6-dimethylpyridazine-3-carboxylic acid PA0 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-5,6-dimethylpyridazine-3-carboxylic acid PA0 1-phenyl-1,4-dihydro-4-oxo-5-ethyl-6-methylpyridazine-3-carboxylic acid PA0 1-phenyl-1,4-dihydro-4-oxo-5,6-diethylpyridazine-3-carboxylic acid PA0 1-(4-methylphenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(2,4,6-trichlorophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(3-ethoxyphenyl)-1,4-dihydro-4-oxo-6-ethylpyridazine-3-carboxylic acid PA0 1-(4-methylthiophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(3-cyanophenol)-5-bromo-1,4-dihydro-4-oxo-6-ethylpyridazine-3-carboxylic acid PA0 1-phenyl-5-bromo-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid PA0 1-(3-chlorophenyl)-5-chloro-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxyl ic acid PA0 1-(4-chlorophenyl)-5-bromo-1,4-dihydro-4-oxo-6-ethylpyridazine-3-carboxylic acid, PA0 1-(2-chloro-4-methyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid, PA0 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-6-phenylpyridazine-3-carboxylic acid PA0 1-(4-trifluoromethylphenyl)-1,4-dihydro-4-oxo-5-phenethyl-6-methylpyridazin e-3-carboxylic acid PA0 1-(3,4-dichlorophenyl)-1,4-dihydro-4-oxo-6-butylpyridazine-3-carboxylic acid PA0 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-5,6-cyclohexa[b]-pyridazine-3-carboxyl ic acid PA0 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-5-propyl-6-methylpyridazine-3-carboxyl ic acid PA0 1-phenyl-1,4-dihydro-4-thio-6-methylpyridazine-3-carboxylic acid PA0 1-(3-chlorophenyl)-1,4-dihydro-4-thio-6-ethylpyridazine-3-carboxylic acid
and the like,
and the salts, esters and amides of the above acids.
The compounds of the invention can be prepared by several convenient preparative routes. In the first method, a 4-hydroxy-2-pyrone of the formula ##STR5## wherein R.sup.3 is a hydrogen atom, an aralkyl group or an alkyl group and R.sup.2 is defined above, or a salt of a pyrone of Formula II, prepared by treating the pyrone with an equivalent of a suitable aqueous base such as potassium or sodium hydroxide, acetate, or carbonate, is reacted at about -10.degree. to about 50.degree. C. in a polar solvent, such as water, methanol, ethanol, glyme, dimethylformamide, or the like, with a diazonium salt, such as diazonium chloride prepared by conventional diazotization technique from an amine of the formula EQU R.sup.1 --NH.sub.2 (III)
wherein R.sup.1 is as defined above. The product hydrazone, which has the formula ##STR6## wherein R.sup.1, R.sup.2, and R.sup.3 are as defined above, is then treated with either an aqueous acid, such as hydrochloric acid, trifluoroacetic acid, sulfuric acid, methanesulfonic acid, nitric acid, or the like, or an aqueous base, such as sodium carbonate, sodium hydroxide, or an alcoholic secondary amine such as morpholine, piperidine, dialkyl amine and the like, at a temperature of about 0.degree. to about 150.degree. C., preferably about 40.degree. to about 100.degree. C., to yield, by a rearrangement, a pyridazinone of the formula ##STR7## or salt thereof wherein R.sup.1, R.sup.2, and R.sup.3 are as defined above.
The pyridazinones of the invention in which R.sup.3 is a halogen atom can be prepared by reacting the corresponding pyridazinones in which R.sup.3 is a hydrogen atom with one equivalent of a halogenating agent such as bromine, chlorine, sulfuryl bromide, sulfuryl chloride, or the like in a suitable inert solvent such as hexane, benzene, ethylene dichloride, methanol, or the like, at a temperature of about 0.degree. to 50.degree. C., preferably at room temperature.
Salts of the pyridazinones of Formula V and their 5-halo analogues can be prepared by conventional techniques, such as by neutralization with an appropriate inorganic or organic base, in a solvent such as water or methanol.
Esters of the pyridazinone of Formula V are prepared by esterification with a suitable alcohol, preferably a (C.sub.1 -C.sub.12)alkanol. One convenient technique is a Fischer esterification, using anhydrous hydrochloric acid or sulfuric acid as a catalyst and the alcohol as the solvent. This esterification is generally carried out at about 35.degree. to about 150.degree. C., optionally using an inert cosolvent such as methylene chloride, ethylene chloride, diethyl ether, toluene, xylene, or the like.
Another convenient esterification technique is the reaction of the pyridazinone acylhalide formed as above with an appropriate alcohol utilizing the alcohol or any inert cosolvent for the reaction media. Alternatively a thionyl halide can be utilized to first form a halosulfinite with the appropriate alcohol and this halosulfinite can then be reacted with the pyridazinone carboxylic acid to form the appropriate ester. These esterification procedures can be carried out at about 0.degree. to about 80.degree. C. The alcohol of the ester can also be used as the solvent in this Reaction.
Yet another esterification technique involves the use of a halo carboxylate to form a pyridazinone acylanhydride followed by either thermal decomposition to eliminate carbon dioxide and form the desired ester or addition of an equimolar (or excess) amount of the alcohol of the ester, to form the desired ester. This reaction can iritially be run at about 0.degree. C. and the temperature increased until the evolution of carbon dioxide has ceased. This reaction is carried out in the presence of an acid scavenger in an inert solvent. The thioesters of the invention can be prepared as above by the replacement of a thioalcohol.
The pyridazinone carbamides of the invention can be prepared by standard synthetic routes such as the reaction of the acylhalide discussed above with an appropriate amine in an inert solvent at about 0.degree. to about 150.degree. C. Another convenient amination route utilizes the reaction of the pyridazinone carboxylic acid with an appropriate halocarboxylate to first form an acylanhydride which in turn is reacted with an appropriate amine at temperature at about 25.degree. to about 110.degree. C. in an iner solvent again with the evolution of carbon dioxide to form the appropriate carbamide.